Major nuclear envelope abnormalities, such as disruption and/or presence of intranuclear organelles, have rarely been described in cardiomyocytes from dilated cardiomyopathy (DCM) patients. In this study, we screened a series of 25 unrelated DCM patient samples for (a) cardiomyocyte nuclear abnormalities and (b) mutations in LMNA and TMPO as they are two DCM-causing genes that encode proteins involved in maintaining nuclear envelope architecture. Among the 25 heart samples investigated, we identified major cardiomyocyte nuclear abnormalities in 8 patients. Direct sequencing allowed the detection of three heterozygous LMNA mutations (p.D192G, p.Q353K and p.R541S) in three patients. By multiplex ligation-dependant probe amplification (MLPA)/quantitative real-time PCR, we found a heterozygous deletion encompassing exons 3-12 of the LMNA gene in one patient. Immunostaining demonstrated that this deletion led to a decrease in lamin A/C expression in cardiomyocytes from this patient. This LMNA deletion as well as the p.D192G mutation was found in patients displaying major cardiomyocyte nuclear envelope abnormalities, while the p.Q353K and p.R541S mutations were found in patients without specific nuclear envelope abnormalities. None of the DCM patients included in the study carried a mutation in the TMPO gene. Taken together, we found no evidence of a genotype-phenotype relationship between the onset and the severity of DCM, the presence of nuclear abnormalities and the presence or absence of LMNA mutations. We demonstrated that a large deletion in LMNA associated with reduced levels of the protein in the nuclear envelope suggesting a haploinsufficiency mechanism can lead to cardiomyocyte nuclear envelope disruption and thus underlie the pathogenesis of DCM.

Objective To obtain a greater understanding of the pathogenesis of endometrial polyps and to gain insight into which factors play a pivotal role in their growth. Design Retrospective analysis of archived paraffin-embedded specimens.

The fear of cancer is ubiquitous and simple; until very recently, cancer was always synonymous with death. Yet like cancer itself, the stigmatization of cancer is complex and heterogeneous. That is, although cancer in general is feared and still stigmatized for its legacy as a lethal disease, specific cancers are stigmatized for different reasons. A variety of factors influence why certain types of cancer are more stigmatized than others; this occurs in part because different cancer types have different causes, different treatments, and different outcomes. Whereas cancer stigma takes many forms, the outcomes of the stigma are most often negative. For example, public stigma of cancer can present a barrier to treatment and lead to social isolation, as patients are "outed" by treatment side effects (e.g., alopecia) and avoided by friends and loved ones (Herek, 1999;Lebel & Devins, 2008). Structural stigma, which occurs when agencies restrict funds for screening and treatment of cancers stigmatized as cAncer STigmA nicoLe m. eLSe-QueST AnD TrAcY L. JAckSonWe are grateful to Heidi Hamann for comments on a previous draft.

Fewer endometrial abnormalities occurred during 2 years treatment with anastrozole compared with tamoxifen although statistical significance was not reached in this sub-protocol analysis.

al. Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A.

CYP3A4-mediated drug interactions represent a significant risk in patients treated with long-term inhaled corticosteroids. The presence of clinically significant CF-related liver disease may enhance this risk.

During June and July 1999, oral interviews were conducted on 666 women seeking prenatal care at 9 medical facilities in Chennai and Mysore, India, to assess their attitudes towards prenatal HIV testing and antiretroviral prophylaxis for preventing perinatal HIV transmission if needed. Seventy-eight per cent were aware of the risk of perinatal HIV transmission and 36% knew that intervention could reduce the chances of such transmission. Eighty-six per cent would agree to undergo prenatal HIV testing but only 21% of all respondents would make this decision independently while 46% said their husband would have to decide. Of those women who would not agree to testing, 21% would agree if testing were compulsory. Ninety-seven per cent of respondents would undergo antiretroviral prophylaxis to prevent vertical transmission, and 94% would consider alternatives to breastfeeding if HIV positive. Considering its widespread acceptability, prenatal voluntary counselling and testing may be an affordable method of HIV prevention for this population.

On behalf of The ATAC Trialists' GroupObjective The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial is a randomised, double-blind trial comparing 'Arimidex' (anastrozole), alone or in combination with tamoxifen, relative to tamoxifen alone as a five year adjuvant treatment for postmenopausal women with early breast cancer. Because tamoxifen is associated with endometrial pathology, the ATAC endometrial subprotocol was initiated to establish the background prevalence of pathology, and to assess prospectively the incidence and nature of intrauterine changes before and following endocrine therapy. Setting International.Population and Study Design Two hundred and eighty-five women entered the subprotocol: the mean age was 60 years (range 44-80 years); 113 women (40%) had taken hormone replacement therapy prior to randomisation, and 238 women were parous (84%). The age at onset of the menopause was 32-58 years, with the majority becoming menopausal between 46 and 55 years of age. Two hundred and seventy-two women had a hysteroscopy before they commenced trial medication. Hysteroscopy was performed successfully in 265 women. In six women, failure of hysteroscopy at baseline led to withdrawal from the study. Three of the women who withdrew had a pipelle biopsy taken. Therefore, the total number of endometrial biopsies at baseline was 268. Main outcome measures To assess the demographic characteristics of women entering the endometrial subprotocol and their hysteroscopic and histological findings before commencing trial medication. Results At hysteroscopy, there was a diagnosis of endometrial polyps in 34 women (13%), fibroids in 16 women (6%) and one case of suspicious endometrium, which was confirmed as a polyp on histology. Only 21 of the 34 polyps seen hysteroscopically were proven histologically (62% accuracy of hysteroscopy).Final histology found the prevalence of endometrial diagnostic categories as follows: 123 inactive endometrium (46%), 20 benign polyps (7%), 17 secretory endometrium (6%), 7 proliferative endometrium (3%), 3 atypical hyperplasia (2 in a polyp), 1 simple hyperplasia (in a polyp) and 1 fibroid. The remaining women had pipelle samples with insufficient tissue obtained, indicating a normal endometrial cavity. Conclusion This is the first study of such size in gynaecologically asymptomatic breast cancer patients. This paper describes the findings in individual patients before any trial treatment was given. In this baseline group, 82% (219/268) of women had a normal endometrial cavity; 18% (49/268) had endometrial activity (proliferative or secretory endometrium in 9%) or an intracavity abnormality (hyperplasia, polyps and a fibroid in 9%). In total, 36% of biopsies had insufficient tissue for diagnosis, which in combination with a normal hysteroscopy was classed as normal. The appearance of a polyp hysteroscopically in this group was not proven histologically in approximately 40% of cases. The development of uterine pathology over time in the ATAC study will subsequently be assessed again...